Rare gene variants passed on from parents may significantly increase risk of autism

NEW YORK — Autism’s cause is not something science has completely figured out yet. Studies have discovered several different links which appear to play a role in children developing the condition. Now, researchers have identified a rare a class of genetic differences which parents without autism pass on to their children. The study finds these variants make it significantly more likely the child with develop autism.

A team working with the Simons Foundation in New York adds this hereditary link is especially prominent among “multiplex” families, where other members of that family have autism, even if the parents of that particular child do not.

New technology reveals new gene ties to autism

Study authors, led by Amy B. Wilfert, Ph.D. from the University of Washington, say new technology and dropping costs on genetic research has allowed them to gather information of thousands of genes from people with autism and their relatives. Researchers analyzed nearly 11,000 people with autism to identify the new mutations which pass (or over-transmit) from healthy parents to children on the autism spectrum.

The team notes most autism genes discovered to date come from research on de novo mutations. These are genetic variations which first develop in a person with autism and are not present in their parents’ genes at all. The new findings reveal that rare inherited variants which lead to autism are likely in a different batch of genes from the ones de novo mutations affect.

“While most autism studies focus on de novo mutations, this study focuses on rare inherited mutations, which are often understudied in autism,” says Dr. Wilfert in a media release. “We find that these variants are individually less damaging than de novo mutations but have the potential to contribute almost as much risk and impact the same molecular pathways, through a distinct set of genes. These variants, however, are only able to persist in the general population for a few generations before being selected out by evolution.”

“It is widely understood that de novo mutations cannot and do not explain all of the genetic causes of autism, a phenomenon sometimes referred to as ‘missing heritability,'” adds Pamela Feliciano, Ph.D., the scientific director of SPARK (Simons Powering Autism Research).

Are a whole new batch of genes leading to autism?

The SPARK Consortium contributed more than half of the genetic data researchers used for this project. In total, the team reviewed genetic material from over 21,000 SPARK participants, including more than 6,500 with autism spectrum disorder (ASD). Despite knowing about many genes and mutations which show a connection to autism, the results reveal these new “ultra-rare inherited variants” are not coming from the typical pool of autism genes.

“Interestingly, the vast majority of those variants (95%) are not found in genes already known to be autism genes, indicating that there is much more to be learned about autism genetics,” says Dr. Feliciano. “While the current study is not large enough to confidently identify individual genes that have these rare inherited variants, we are learning more about these genes. Future research that focuses on multiplex families is increasingly important to yield novel insights.”

Moreover, the study also confirmed that children with ASD are more likely to carry two of these inherited mutations in comparison to their siblings without autism.

According to the CDC, around one in 54 children in the United States will develop ASD. Most children on the spectrum will receive a diagnosis by age three, but some doctors may be able to see the signs before a child turns 18 months-old. Some of the early signs of autism include avoiding eye contact, lack of interest in other children and caregivers, and displaying limited language skills.

The findings appear in the journal Nature Genetics.